IVTA as adjunctive treatment to PRP and MPC for PDR and macular oedema: a meta-analysis

Methodological quality of the review: Medium confidence

Author: Liu L, Wu X, Geng J, Yuan Z, Chen L.

Region: Europe, Asia, South America.

Sector: Diabetic Retinopathy, Diabetic macular oedema

Sub-sector: Intravitreal triamcinolone acetonide (IVTA) injection, panretinal photocoagulation (PRP)

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis methods: Not applicable

Background           

A previous study demonstrated that intravitreal triamcinolone acetonide (IVTA) injection may improve inflammatory, oedematous, and neovascular ocular conditions and that it has also been used to treat macular oedema combined with macular photocoagulation (MPC). A hypothesis was formed that IVTA injection may have an additive effect with the standard treatment, panretinal photocoagulation (PRP) and MPC, with respect to visual acuity (VA) improvement, and central macular thickness (CMT) reduction. Studies were carried out to clarify this, but the conclusions were inconsistent.

Research objectives

To quantify the effect of a combination treatment of intravitreal triamcinolone acetonide (IVTA) injection, panretinal photocoagulation (PRP), and macular photocoagulation (MPC) in patients with proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DME).

Main findings

After a systematic review of the 32 eligible studies, only four were ultimately included in the meta-analysis. One of the trials was performed in Europe, two in Asia, and the last one was in South America.  Based on the Jadad scoring system, overall included studies were of high quality; two studies scored 4, one study score 5 and one scored 3.

Authors reported the following results:

Treatment with IVTA injection combined with PRP and MPC significantly improved BCVA (p< 0.001) from one to six months, compared with PRP and MPC alone. There was a statistically significant mean difference in central macular thickness (CMT), at the one-month follow-up (p< 0.001). No evidence of publication bias was present. There was a low level of heterogeneity in this group of studies.

Based on these findings authors concluded: ‘This meta-analysis indicates that IVTA injection combined with PRP and MPC results in an improvement of BCVA, and CMT reduction in patients with PDR and DME’. Authors mentioned that randomized controlled trials (RCTs) with larger sample sizes, possibly multicentre trials, and longer follow-up times were needed to better evaluate the benefits and safety of IVTA injection combined with PRP and MPC for PDR and DME.

Methodology

Authors included RCTs which evaluated IVTA injection combined with PRP and MPC treatment for PDR; at least one or more clinical outcome parameters had to have been assessed and published. Outcome measures considered for this review included:  BCVA of logarithm of the minimum angle of resolution (logMAR) units, CMT, intraocular pressure (IOP), standard central macular thickness (SCMT), total macular volume (TMV). Any changes in VA compared with the pre-injection level, and complications after therapy, were evaluated following IVTA injection combined with PRP and MPC for treatment of PDR and DME in the various outcomes from the different articles.

Two authors independently searched the following electronic databases: MEDLINE (1950 to April 2012), EMBASE (1998 to April 2012), Web of Science, Google Scholar (10 April 2012) and the Cochrane Library, with no language restrictions applied. A manual search of bibliographies was also performed. All published articles that were internet accessible were considered. Authors extracted data from each study using a standardized form including: (1) general data: title, authors, publication date, resource; (2) subjects, intervention measures, quality control; and (3) outcomes.

Methodological quality was assessed by methods of random allocation, allocation sequence concealment, blinding and missing outcome data on follow-up using the Jadad Score. High quality was defined as a Jadad score more than three.

Authors conducted a meta-analysis according to a predetermined protocol described previously in QUOROM statement and MOOSE recommendations.

Applicability/external validity

The authors did not discuss the applicability/external validity of the review.

Geographic focus

The review focussed on Europe, Asia and South America. The results presented in the review did not discriminate between countries as all studies were pooled together for analysis; nevertheless, the results were clinically useful for treatment considerations.

Quality assessment

A medium confidence was attributed in the conclusions about the effects of this study as limitations were identified in the review. Authors used appropriate criteria in terms of literature search avoiding language bias.  Nevertheless, it was not clear from the review if study selection, data extraction and quality assessment of included studies were conducted by two reviewers independently.

The authors acknowledged the following limitations within the study: only a small number of trials were enrolled in this meta-analysis, these were short and included different follow-up times for observation and only two common outcomes were evaluated. They also noted that publication bias could not be fully excluded as the authors could not attempt to gain access to unpublished articles.